Improving the Representativeness of Behavioral and Clinical Surveillance for Persons with HIV in the United States: The Rationale for Developing a Population-Based Approach

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services

Development of high strength self-compacting fibre reinforced concrete for prefabricated concrete industry

Prefabricated construction is an emerging industry in Australia and considered a key mechanism to boost productivity in the construction industry. The use of fibre reinforced concrete has a huge potential in the prefabricated industry as the concrete can be delivered straight to the precast mould, eliminating in many cases the steel reinforcement, thus increasing production quotas and cost savings. Such results can be further improved by utilising self-compacting concrete reinforced with fibres. Although the use of steel fibres as reinforcement is now well established, in the precast industry thin walls and shape of the moulds can be a limitation to steel fibre as well as work health and safety concerns for handling. Under such conditions, the use of polymeric fibres can be extremely beneficial, reducing labour hours and placement time as well as improving safety. This paper reports the development of high strength self-compacting fibre reinforced concrete for application in prefabricated concrete industry, exploring the effect of Forta-Ferro and ReoShore fibres on concrete fresh and mechanical properties

Substance Use Disorders in Adolescent and Young Adult Relatives of Probands with Bipolar Disorder: What Drives the Increased Risk?

Background Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. Methods We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006–2011. Youth offspring/relatives (“Relatives of BD probands;” n = 267; mean age = 16.8 years; ± 2.9 S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands (“relatives of control probands;” n = 149; mean age = 17.4 years; ± 2.9 S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. Results Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p = 0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR = 2.80–3.17; p < 0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. Conclusion Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population

A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders

CONTEXT: The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy. OBJECTIVE: To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects. DESIGN: A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures. SETTING: Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009. PARTICIPANTS: Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91). MAIN OUTCOME MEASURE: Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression). RESULTS: At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders. CONCLUSIONS: Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP

The Lunar Polar Hydrogen Mapper (LunaH-Map) Mission

The Lunar Polar Hydrogen Mapper (LunaH-Map) mission will map hydrogen enrichments within permanently shadowed regions at the lunar south pole using a miniature neutron spectrometer. While hydrogen enrichments have been identified regionally from previous orbital missions, the spatial extent of these regions are often below the resolution of the neutron instruments that have flown on lunar missions. LunaH-Map will enter into an elliptical, low altitude perseline orbit which will enable the mission to spatially isolate and constrain the hydrogen enrichments within permanently shadowed regions. LunaH-Map will use a solid iodine ion propulsion system, X-Band radio communications through the NASA Deep Space Network, star tracker, C&DH and EPS systems from Blue Canyon Technologies, solar arrays from MMA Designs, LLC, mission design and navigation by KinetX. Spacecraft systems design, integration, qualification, test and mission operations are performed by Arizona State University

LunaH-Map: Revealing Lunar Water with a New Radiation Sensor Array

A new type of neutron and gamma-ray spectrometer called the Miniature Neutron Spectrometer (Mini-NS) has been developed, assembled, qualified and delivered as part of the Lunar Polar Hydrogen Mapper (LunaH-Map) cubesat mission. The LunaH-Map spacecraft is currently manifested as a secondary payload on the Space Launch System (SLS) Artemis-1 rocket. LunaH-Map will deploy from Artemis-1 and enter a low altitude perilune elliptical orbit around the Moon. The Mini-NS will measure the lunar epithermal neutron albedo, and measurements around perilune will be used to produce maps of hydrogen enrichments and depletions across the lunar South Pole region including both within and outside of permanently shadowed regions (PSRs). The Min-NS was designed to achieve twice the epithermal neutron count rate of the Lunar Prospector Neutron Spectrometer (LP-NS). The instrument response was characterized through the collection of pre-flight neutron counting data with a Cf-252 neutron source at Arizona State University across hundreds of power cycles, as well as across the expected temperature range. The instrument spatial response was characterized at the Los Alamos National Laboratories (LANL) Neutron Free In-Air Facility. The LunaH-Map Mini-NS was designed to fit within the cubesat form-factor and uses two detectors with eight sensor heads that can be operated independently. For future missions with different science goals that can be achieved with epithermal neutron detection, the number of Mini-NS sensor heads can easily be modified without requiring a complete re-design and re-qualification

Evolution records a Mx tape for anti-viral immunity

Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and species-specific susceptibility to viral infection

Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure.</p> <p>Methods</p> <p>We sequenced <it>CHRNA1</it>, <it>CHRND </it>and <it>CHRNG </it>in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS).</p> <p>Results</p> <p>The minor allele of a synonymous coding SNP, rs2099489 in <it>CHRNG</it>, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations).</p> <p>Conclusion</p> <p><it>CHRNG </it>is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.</p

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

Genome-Wide Association Analysis of Ischemic Stroke in Young Adults

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults